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Nucleic acids: DNA and RNA

Done By

Majed Felemban

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DNA

• Double helix– 2 chains

• Building blocks– Nucleotides

• DNA directs– Is own replication– Directs RNA synthesis → protein synthesis

Campbell and Reece, P86

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In Eukaryotes (animals, plants, fungi)

Complete human genome

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In Prokaryotes (bacteria, archaea)

• Main chromosome is one large, continuous loop– Hundreds to thousands

of genes

• May have smaller loops, with a few genes each– May be swapped

between bacteria– Antibiotic resistance, etc.

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Replication

Transcription

Translation

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Roles of Nucleic Acids• DNA

– Responsible for inheritance– Codes for proteins and functional RNAs

• Genes

– Regulatory sequences• Control which genes are transcribed, and when

– Other unknown functions• 80-90% of the human genome has no known function

Campbell and Reece, P86, 87

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Roles of Nucleic Acids• RNA

– Information transmission (mRNA)– Processing and transport (tRNA, rRNA, snRNA)– Catalytic (ribozymes)– Regulation and feedback (siRNA)– Unit of inheritance (retroviruses)– Other…?

Campbell and Reece, P86, 87

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• Nucleic Acid chemistry is the same for all life on earth.• DNA & RNA are polymers of monomers - nucleotides.• Each nucleotide has three components

(Deoxy)ribonucleic Acid

NUCLEIC ACID STRUCTURES

Campbell and Reece, 86

OH

O-

O

PO-

O

O-

O

PO- OH

O

OHOH

O

O-

O

PO- N

O

OHOH

N

NN

NH2

2. (DEOXY)RIBOSE SUGAR = STRUCTURAL

3. NITROGENOUS BASES = INFORMATIONAL

O

O

O

PO- N

O

OHO

N

NN

NH2

O NO

OH

O

O

PO-

X

X

1. PHOSPHORIC ACID = STRUCTURAL

9Campbell and Reece, P87

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Phosphoric Acid & Related Compounds

• Phosphoric acid isTriprotic.

• Reacts with CHO’s or alcohols to form esters.

D

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Phosphoric Acid & Related Compounds

• Phosphoric acid isTriprotic.

• Reacts with alcohols to form esters.

As found in DNA& RNA at pH7

-

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The sugar may be Ribose (in RNA) or Deoxyribose (in DNA)

H

Ribose Deoxyribose

Phosphate can covalently bond to C3 and C5

Bases (A,C,G,T or U) can covalently bond to C1

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Bases in DNA and RNA

(RNA) (DNA)

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A Base Joined To A Ribose SugarIs Called A Nucleoside

Pyrimidines bond at N-1 to C-1’

Purines bond N-9 to 1’ Carbon of sugar

The carbons in the ribose are now designated as C prime (or C’) to distinguish them from those in the base.

or H

or H

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When Phosphate is Bound to a Nucleoside it is Called a Nucleotide

• ATP, GTP, CTP, UTP (NTPs) are substrates for RNA synthesis• dATP, dGTP, dCTP, dTTP (dNTPs) are substrates for DNA synthesis

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Mononucleotides as they Occur in DNA & RNA

DNA

RNA

A,C,G or T (DNA)orA,C,G or U (RNA)

All nucleotides are asymmetrical

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5’C =

Four Nucleotides With 5’ to 3’ Phosphodiester Linkages

3’C =

DNA & RNA are Polymers of Nucleotides

All DNA and RNA polymers are asymmetrical with 5’ to 3’ direction.

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Properties of DNA and RNA

• They may be informational eg genomic DNA, mRNA.

• They may be structural eg rRNA & tRNA.

• Retain 5’& 3’ molecular orientation due to nucleotide asymmetry.

• They are often single stranded (typically RNA).

• They may be extremely long. Movie*

• Two polymers (or strands) may become double stranded when

certain conditions are met ie they are antiparallel &

complementary in nucleotide sequence (typically nuclear DNA).

* Terao et al., 2008: Lab on a chip DOI: 10.1039/b803753a

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Duplex DNA is Antiparallel

Duplex DNA is NEVER Parallel!

5’Phosphate

3’OH

3’OH

5’Phosphate

or

5’3’

3’

5’

or

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Duplex DNA has Complementarity because of Hydrogen Bonds

• H bonds are weak (~1/20th of a covalent bond):– Often allows transient contact between molecules (biological

signalling systems).– May allow stable contact that can be disrupted and reformed (eg

DNA).

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Hydrogen Bonds

• Form between O &/or N with H between them

eg O-H…O, N…H-N or O-H…N.

• Are due to electrostatic forces.

H is slightly +ve.

O &/or N are slightly -ve.

• Are very weak compared to covalent bonds

• May be broken & reform under various chemical or physical conditions.

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Two representations of duplex DNA showing:

• H bonds between bases and,

• Covalently bonded Sugar Phosphate backbones.

• ~10 basepairs per turn of the helix.

• Duplex DNA width = 2nm.

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Double Stranded (or Duplex) DNA

• Is characteristic of genomic DNA.

• Consists of two separate nucleic acid polymers (“strands”).

• The two strands are Antiparallel wrt 5’& 3’ ends.

• They are held together by Hydrogen Bonds between the bases.

• H-Bond energies are weak BUT there are many of them which makes the duplex DNA very stable.

• Bases are Complementary such that:

– A always pairs with T (2 H Bonds).

– C always pairs with G (3 H Bonds).

• Two strands of complementary antiparallel DNA form a Double Helix eg as found in a chromosome.

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History of The Double Helix of DNA

• The structure of the double helix was found by Rosalind Franklin using X-ray crystallography and correctly interpreted by Watson & Crick in 1953 who also used Chargaff’s rule.

• The bases are Hydrophobic and are in the Centre of the helix where complementary bases pair via H-bonding.

• The Ribose Sugar and Phosphate groups are on the Outside of the helix where they can H bond to polar solvents like water.

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Xray diffraction pattern of DNA similar to Franklin’s data (above, 1953).

Watson & Crick’s structure for DNA

Key data that Watson & Crick worked with

Chargaff’s Rule: there is a 1:1 ratio of purines to pyrimidines (because A=T, GC always).

1GATC